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BACKGROUND: Sexual health is understudied and underreported in patients with lung cancer, and most data precede the approval of widely used targeted therapies and immune checkpoint inhibitors. The authors sought to evaluate the prevalence of sexual dysfunction in women with lung cancer in our current clinical environment. METHODS: This cross-sectional survey study was administered online to 249 women via the GO2 for Lung Cancer (GO2) Registry, using the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Measures questionnaire. Participants were recruited between June 2020 to June 2021. Eligibility criteria included age >18 years, self-identifying as a woman, fluency in English, and a lung cancer diagnosis within 10 years. RESULTS: Most (67%) had stage IV lung cancer and 47% were receiving targeted therapy; 66% were undergoing active treatment. Despite 54% of participants reporting "recent" sexual activity, most (77%) indicated having little to no interest in sexual activity and 48% reported recent minimal satisfaction with their sex life. The most common reasons negatively affecting participants' satisfaction with their sex life included fatigue (40%) and feeling sad/unhappy (28%). Common reasons for lack of recent sexual activity included lack of interest (68%) and vaginal dryness or pain (30%). Compared to pre-diagnosis, women were significantly less likely to have recent interest in sexual activity. In multivariable logistic-regression, vaginal dryness showed a significant negative association with recent interest in sexual activity. CONCLUSIONS: Sexual dysfunction is prevalent in women with lung cancer. Sexual health should be integrated into routine care for patients with lung cancer.
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Neoplasias Pulmonares , Disfunciones Sexuales Fisiológicas , Salud Sexual , Enfermedades Vaginales , Humanos , Femenino , Adolescente , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Estudios Transversales , Conducta Sexual , Encuestas y Cuestionarios , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Fisiológicas/etiologíaRESUMEN
BACKGROUND: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. METHODS: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. RESULTS: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30-day and 90-day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). CONCLUSION: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30-day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population.
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Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Anciano , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/cirugía , Quimioradioterapia , Tiempo de Internación , Terapia Recuperativa , LaringectomíaRESUMEN
We present the case of a patient with oral squamous cell carcinoma treated with the programmed death ligand inhibitor, pembrolizumab, an immune checkpoint inhibitor. She subsequently developed vasovagal-type autonomic dysfunction thought to be secondary to the pembrolizumab. The patient's vasovagal symptoms resolved with the initiation of oral glucocorticoids.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Disautonomías Primarias , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico , Carcinoma de Células Escamosas/tratamiento farmacológicoRESUMEN
BACKGROUND/AIM: There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examined the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies. PATIENTS AND METHODS: We performed a retrospective review on an IRB-approved dataset of patients with sinonasal malignancies treated at a single institution between 2005 to 2021. Patients were categorized into groups based on the frequency of annual imaging and total number of imaging studies. We compared time-to-recurrence between the groups using log-rank test. A two-sided p-value of <0.05 was considered as the threshold for significance. RESULTS: A total of 93 patients were eligible for this study with a median follow up of 42.3 months and 25.8% (n=24) of patients had documented recurrence. Sensitivity and specificity for recurrence based on computed tomography (CT) scans within one year of treatment completion were 50.0% and 19.5%; positron emission tomography/CT was 90.0% and 19.5%; and magnetic resonance imaging was 60.0% and 61.0%, respectively. Regardless of the type of imaging, symptomatic presentation after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95%CI=1.06-8.22). The frequency of scans was not associated with the risk of recurrence (HR=0.55; 95%CI=0.23-1.29, p=0.17). Similarly, no association was noted between the total number of scans and risk of recurrence (HR=0.64; 95%CI=0.27-1.51, p=0.31). CONCLUSION: The total number of frequency of scans within the first year after treatment had no association with time to recurrence of sinonasal malignancies. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.
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Neoplasias Nasales , Neoplasias de los Senos Paranasales , Humanos , Neoplasias de los Senos Paranasales/diagnóstico por imagen , Neoplasias de los Senos Paranasales/terapia , Recurrencia Local de Neoplasia/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring FAT1 mutations. This phase II, multicenter trial used a Simon 2-stage design to investigate the efficacy of CDX-3379 and cetuximab in 30 patients with recurrent/metastatic, HPV-negative, cetuximab-resistant HNSCC. The primary endpoint was objective response rate (ORR). Secondary endpoints included ORR in patients with somatic FAT1 mutations, progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled from March 2018 to September 2020. The ORR in genomically unselected patients was 2/30 (6.7%; 95% confidence interval [CI], 0.8-22.1). Median PFS and OS were 2.2 (95% CI: 1.3-3.6) and 6.6 months (95% CI: 2.7-7.5), respectively. Tissue was available in 27 patients including one of two responders. ORR was 1/10 (complete response; 10%; 95% CI 0.30-44.5) in the FAT1-mutated versus 0/17 (0%; 95% CI: 0-19.5) in the FAT1-wildtype cohorts. Sixteen patients (53%) experienced treatment-related adverse events (AEs) ≥ grade 3. The most common AEs were diarrhea (83%) and acneiform dermatitis (53%). Dose modification was required in 21 patients (70%). The modest ORR coupled with excessive, dose-limiting toxicity of this combination precludes further clinical development. Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the FAT1 hypothesis warrant consideration.
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BACKGROUND: First-line treatment for patients with non-small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor (EGFR) mutation is a tyrosine kinase inhibitor (TKI). Despite higher response rates and prolonged progression free survival (PFS) compared with platinum doublet chemotherapy, a subset of these patients do not receive prolonged benefit from these agents. We investigate if the neutrophil-to-lymphocyte ratio (NLR) and other markers of cachexia and chronic inflammation correlate with worse outcomes in these patients. METHODS: This study is a retrospective review of 137 patients with advanced EGFR-mutated NSCLC treated with TKIs at Rush University Medical Center and University of Chicago Medicine from August 2011 to July 2019, with outcomes followed through July 2020. The predictive value of NLR and body mass index (BMI) was assessed at the start of therapy, and after 6 and 12 weeks of treatment by univariable and multivariable analyses. RESULTS: On univariable analysis, NLR ≥ 5 or higher NLR on a continuous scale were both associated with significantly worse PFS and overall survival (OS) at treatment initiation, and after 6 or 12 weeks of treatment. On multivariable analysis, NLR ≥ 5 was associated with increased risk of death at 12 weeks of therapy (HR 3.002, 95% CI 1.282-7.029, p = 0.011), as was higher NLR on a continuous scale (HR 1.231, 95% CI 1.063-1.425, p = 0.0054). There was no difference in PFS and OS and amongst BMI categories though number of disease sites and Eastern Cooperative Oncology Group (ECOG) performance status was associated with worse PFS and OS. CONCLUSIONS: Patients with NLR ≥ 5 have a worse median PFS and median OS than patients with NLR < 5. NLR may have value as a predictive biomarker and may be useful for selecting patients for therapy intensification in the front-line setting either at diagnosis or after 12 weeks on therapy. NLR needs to be validated prospectively.
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BACKGROUND: Durable tumor regressions are observed in a subset of advanced-stage non-small cell lung cancer (NSCLC) patients receiving PD-1/-L1 targeted immune checkpoint inhibitors (or 'immunotherapy') alone or in combination with chemotherapy. However, the majority of advanced NSCLC patients receiving these agents do not experience long-term disease control. Existing methods to identify patients most likely to gain clinical benefit from PD-1/-L1 immunotherapy have limitations, creating a need for improved methods to guide treatment selection, particularly for those likely to benefit from single-agent immunotherapy. Here, we describe the development of a series of novel assays for tumor-associated autoantibodies as part of an exploratory study intended to determine if these biomarkers have potential prognostic value in this setting. METHOD: A selection of recombinant tumor autoantigens previously characterized for their diagnostic utility were developed and preliminarily evaluated by this study. These include: Fumarate Dehydrogenase (FH), Hydroxysteroid 17-Beta Dehydrogenase 10 (HSD17B10), Inosine Monophosphate Dehydrogenase 2 (IMPDH2), New York Esophageal Squamous Cell Carcinoma-1 (NY ESO-1), Phosphoglycerate Mutase 1 (PGAM1), and Vimentin. Custom Luminex immunobead assays were developed for these targets to quantitatively assess autoantibody levels in individual patient sera. Assays were erected as indirect immunoassays on MagPlex® Microspheres using standard carbodiimide/NHS-based chemistries, utilizing a biotin-conjugated secondary (i.e. anti-human IgG) antibody and R-phycoerythrin-conjugated streptavidin reporter system. Standard curves were created for quantitative purposes using commercially-available anti-antigen antibodies and permitted analytical performance characteristics to be calculated. These assays were used to preliminarily evaluate a series of pretreatment serum samples from stage IV NSCLC patients receiving anti PD-1/-L1 therapy after failure of at least one prior line of therapy (n = 40) and their classification efficiency calculated based on 12 months overall survival (OS) threshold. RESULTS: Six assays were developed that each showed dynamic ranges of four orders of magnitude and provided more than 90% classification accuracy based on the observed clinical outcome data. Inter- and intra-assay precision was assessed within these standards and overall %CVs of ≤7% and ≤ 10%, respectively, were calculated. Generally, the baseline level of autoantibodies were significantly (p < 0.05) lower in the ≥12 months survival group relative to the <12 months survival groups. Serum titers of FH, HSD170B, NY-ESO-1, and vimentin were significantly correlated with ≥12 month survival (p-value 0.0038, 0.0061, 0.0073, and 0.022, respectively). IMPDH2 and PGAM1 were found to have marginal significance (p-value 0.08 and 0.076, respectively). CONCLUSION: This study demonstrates an efficient and promising means for assessing circulating autoantibody titers that could be useful in selecting advanced NSCLC patients for PD-1/-L1 directed immunotherapy. Further exploration and validation of this paradigm is warranted to further refine current treatment selection methods for this therapeutic strategy.
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Antineoplásicos Inmunológicos/uso terapéutico , Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Inmunoterapia/métodos , Neoplasias Pulmonares/diagnóstico , Antígenos de Neoplasias/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Selección de Paciente , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
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Inmunoterapia/métodos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/uso terapéutico , Inyecciones Intralesiones , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Linfocitos B , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Linfocitos T CD8-positivos/inmunología , Humanos , Inmunidad Celular , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana , Interleucina-10 , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Represoras/genética , Estaciones del Año , Piel , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Escualeno/administración & dosificación , Microambiente Tumoral/efectos de los fármacos , VacunaciónRESUMEN
Lung cancer continues to be a major worldwide health issue, with more than 50% of patients having incurable metastatic disease at diagnosis. Fortunately, the advanced lung cancer treatment landscape is changing rapidly as a result of the positive impact of effective inhibitors of tumor driver mutations, and the more recent discovery that immune modulation with anti-PD-1/PD-L1 monoclonal antibodies results in tumor regression and prolonged survival. While a relatively small subset of lung cancer patients are candidates for inhibitors of driver mutations, the majority of advanced lung cancer patients are candidates for an immunotherapy regimen. Many of these patients have cachexia, which is associated with increased cancer therapy toxicity and possibly reduced responsiveness to immunotherapy. Two ongoing cachexia trials, one testing a ghrelin analogue and the other testing a multimodal strategy, have endpoints which assess clinical benefit-weight gain and relief of anorexia/cachexia symptoms. Provided that the trial objectives are achieved, these treatment strategies will provide a way to relieve suffering and distress for cachectic cancer patients. While awaiting the results of these trials, it would be reasonable to consider designing studies testing cachexia treatments combined with first-line immunotherapy and chemotherapy-immunotherapy in stage IV lung cancer patients, with enhanced overall survival being one of the endpoints.
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BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has a patient demographic, presentation, and clinical treatment response distinct from HPV-unassociated OPSCC. The heterogeneity in presentation and diagnosis within a patient population with HPV-positive OPSCC and its impact on times to presentation, diagnosis, and treatment have yet to be characterized. PARTICIPANTS: Patients with biopsy-proven p16-positive OPSCC seen and/or treated at our institution between 2008 and 2018. Of 136 patients with OPSCC seen and/or treated at our institution, 101 met criteria for inclusion. METHODS: Patients were grouped by several parameters including presenting symptom category (asymptomatic neck mass, neck mass with primary-site symptoms, or primary-site symptoms without a neck mass), p16 status on fine-needle aspiration (FNA), and date of presentation. Median time intervals between presentation to imaging, biopsy, and treatment were compared within each parameter using the Kruskal-Wallis test with a significance level of 0.05. RESULTS: Sixty-five of the 101 study patients presented with a neck mass. Patients without a neck mass had a longer interval from presentation to imaging than patients with a neck mass (median 4 vs 0â¯days, pâ¯=â¯0.025). Initial FNA obtained on 61 patients was positive for p16 in 19 patients. Unknown or negative p16 status on FNA was associated with shorter intervals from initial imaging to treatment initiation (39 vs 46.5â¯days, pâ¯=â¯0.045). Patients presenting in the final three years had a longer interval from presentation to treatment initiation (55 vs 41â¯days, pâ¯=â¯0.024). CONCLUSION: A neck mass is absent from the clinical picture of a substantial proportion of HPV-associated OPSCC patients. Primary-site symptom category and regional metastasis were not associated with differences in times to diagnosis or treatment initiation at this major referral center. The increased awareness and complexity of treatment decisions related to OPSCC may contribute to the delays in treatment initiation observed in patients with p16-positive FNAs and those who presented in more recent years.
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Biopsia con Aguja Fina/métodos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Adulto , Anciano , Carcinoma de Células Escamosas/terapia , Toma de Decisiones Clínicas , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Femenino , Heterogeneidad Genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/terapia , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Estados UnidosRESUMEN
INTRODUCTION: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. METHODS: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. RESULTS: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. CONCLUSIONS: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Receptor de Muerte Celular Programada 1/uso terapéutico , Calidad de Vida/psicología , Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Docetaxel/farmacología , Femenino , Humanos , Neoplasias Pulmonares/patología , MasculinoRESUMEN
OBJECTIVE: The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide. METHODS: Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab. RESULTS: Of the 45 patients enrolled, 56% were male and 22% had treated brain metastases. The median PFS was 1.4 months (95% confidence interval [CI]: 1.3-2.8), with a 1-year PFS of 13%. The median OS was 9.6 months (95% CI: 7.0-12), with a 1-year OS of 37%. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1%) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95% CI: 1.1-12.8) compared with 1.3 months (95% CI: 0.6-2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed. CONCLUSION: Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13% and OS rate of 37% suggest that a subset of patients did benefit from pembrolizumab.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Supervivencia sin Progresión , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes. METHODS: Serum samples were prospectively collected from 57 patients receiving salvage chemotherapy and 70 non-EGFR mutated patients receiving erlotinib. Patients were classified as either VeriStrat good or poor based on the VeriStrat test. Luminex immunoassays were used to measure circulating levels of 102 distinct biomarkers implicated in tumor aggressiveness and treatment resistance. A Cox PH model was used to evaluate associations between biomarker levels and clinical outcome, whereas the association of VeriStrat classifications with biomarker levels was assessed via the Mann-Whitney Rank Sum test. RESULTS: VeriStrat was prognostic for outcome within the erlotinib treated patients (HR = 0.29, p < 0.0001) and predictive of differential treatment benefit between erlotinib and chemotherapy ((interaction HR = 0.25; interaction p = 0.0035). A total of 27 biomarkers out of 102 unique analytes were found to be significantly associated with OS (Cox PH p ≤ 0.05), whereas 16 biomarkers were found to be associated with PFS. Thrombospondin-2, C-reactive protein, TNF-receptor I, and placental growth factor were the analytes most highly associated with OS, all with Cox PH p-values ≤0.0001. VeriStrat status was found to be significantly associated with 23 circulating biomarkers (Mann-Whitney Rank Sum p ≤ 0.05), 6 of which had p < 0.001, including C-reactive protein, IL-6, serum amyloid A, CYFRA 21.1, IGF-II, osteopontin, and ferritin. CONCLUSIONS: Strong associations were observed between survival and VeriStrat classifications as well as select circulating biomarkers associated with fibrosis, inflammation, and acute phase reactants as part of this study. The associations between these biomarkers and VeriStrat classification might have therapeutic implications for poor prognosis NSCLC patients, particularly with new immunotherapeutic treatment options.
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Biomarcadores/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Resistencia a Antineoplásicos , Clorhidrato de Erlotinib/uso terapéutico , Mediadores de Inflamación/sangre , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Grandes/sangre , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteómica , Tasa de SupervivenciaRESUMEN
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79). Known EGFR mutation positive cases were excluded from analysis. Associations of biomarkers with outcome parameters and their differential interaction with treatment for survival outcomes were assessed using multivariate Cox PH analyses. RESULTS: Our EMT-based transcriptomic analysis revealed a range of biological processes associated with angiogenesis, apoptosis, cachexia, inflammation, and metabolism emerging as those most highly associated with patient outcome. These processes were evaluated via surrogate serum biomarkers. A treatment-biomarker interaction analysis revealed that higher pretreatment levels of c-Met signaling biomarkers (i.e. HGF levels), pro-inflammatory/ pro-cachexia (e.g. IL-8, sIL-2Rα, FGF-2) processes and a pro-angiogenic (e.g. TGF-α, IL-8, VEGF) milieu were associated with inferior survival (HR=0.35, 0.29, 0.58, 0.50, 0.61, 0.45, respectively; all p<0.05) for patients receiving chemotherapy, relative to erlotinib. In contrast, high levels of decoy receptor for IL-1, sIL-1RII, and a high tissue vimentin/E-cadherin ratio were associated with a poor OS (HR=3.78; p=0.00055) in the erlotinib cohort. CONCLUSIONS: Contemporary precision medicine initiatives that pair patient tumor characteristics with the optimal therapy type may maximize the use of agents targeting EGFR in the treatment of NSCLC.
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BACKGROUND: To the authors' knowledge, the patterns of care for the radiotherapy-based treatment of patients with stage III to IVB oropharyngeal squamous cell carcinoma (OPSCC) are poorly defined. The objective of the current study was to characterize the use and predictors of chemotherapy with radiotherapy for this population using the National Cancer Database. METHODS: Patients in the National Cancer Database with AJCC (American Joint Committee on Cancer) stage III to IV OPSCC who were treated with radiotherapy between 2003 and 2012 were eligible for analysis. Treatment was defined as radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy (IC). Multivariable regression with multilevel modeling was used to determine predictors of any chemotherapy use and, among patients receiving chemotherapy, the predictors of IC. RESULTS: The majority (90%) of the 30,875 eligible patients received chemotherapy, the majority of whom (71% of the total) were treated with definitive chemoradiotherapy; a sizeable percentage of patients received IC (19% of total). On multivariable regression, younger age, favorable comorbidity status, and more advanced tumor and lymph node disease were found to be independent predictors of any chemotherapy and IC use. Nonwhite patients (odds ratio [OR], 0.71; P<.0001), women (OR, 0.74; P<.0001), and individuals without private insurance were found to be significantly less likely to receive chemotherapy. Patients treated at higher-volume institutions were significantly less likely to receive IC (OR, 0.69; P = .0006). Human papillomavirus status did not appear to independently influence treatment choice. CONCLUSIONS: The vast majority of patients with stage III to IVB OPSCC who were treated with definitive radiotherapy received chemotherapy, which is consistent with high-level data and national recommendations. However, disparities with regard to race, sex, and insurance status emerged thereby requiring additional investigation. The frequent use of IC despite limited supportive evidence warrants research on physician and patient decision making and presents an opportunity to improve evidence-based treatment delivery. Cancer 2017;123:273-282. © 2016 American Cancer Society.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/radioterapia , Anciano , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Femenino , Humanos , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de la radiación , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias/métodos , Neoplasias Orofaríngeas/patología , Papillomaviridae , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virologíaRESUMEN
PURPOSE: To perform a cost-effectiveness analysis of primary chemoradiation therapy (CRT) versus transoral robotic surgery (TORS) for clinical N2, human papillomavirus (HPV)-positive oropharyngeal carcinoma. METHODS AND MATERIALS: We developed a Markov model to describe the health states after treatment with CRT or TORS, followed by adjuvant radiation therapy or CRT in the presence of high-risk pathology (positive margins or extracapsular extension). Outcomes, toxicities, and costs were extracted from the literature. One-way sensitivity analyses (SA) were performed over a wide range of parameters, as were 2-way SA between the key variables. Probabilistic SA and value of information studies were performed over key parameters. RESULTS: The expected quality-adjusted life years (QALYs)/total costs for CRT and TORS were 7.31/$50,100 and 7.29/$62,200, respectively, so that CRT dominated TORS. In SA, primary CRT was almost always cost-effective up to a societal willingness-to-pay of $200,000/QALY, unless the locoregional recurrence risk after TORS was 30% to 50% lower, at which point it became cost effective at a willingness-to-pay of $50-100,000/QALY. Probabilistic SA confirmed the importance of locoregional recurrence risk, and the value of information in precisely knowing this parameter was more than $7M per year. If the long-term utility after TORS was 0.03 lower than CRT, CRT was cost-effective over nearly any assumption. CONCLUSIONS: Under nearly all assumptions, primary CRT was the cost-effective therapy for HPV-associated, clinical N2 OPC. However, in the hypothetical event of a large relative improvement in LRR with surgery and equivalent long-term utilities, primary TORS would become the higher-value treatment, arguing for prospective, comparative study of the 2 paradigms.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia/economía , Neoplasias Orofaríngeas/terapia , Procedimientos Quirúrgicos Robotizados/economía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Análisis Costo-Beneficio , Humanos , Cadenas de Markov , Recurrencia Local de Neoplasia , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae , Años de Vida Ajustados por Calidad de Vida , Radioterapia Adyuvante , Procedimientos Quirúrgicos Robotizados/métodos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Despite several randomized trials, the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma (OPSCC) is controversial. This population-based analysis assessed the overall survival (OS) benefit of induction chemotherapy (IC) for patients with stage III-IVB OPSCC. MATERIALS AND METHODS: Patients in the National Cancer Database with stage III-IVA-B OPSCC treated with curative-dose radiotherapy and IC or concurrent chemotherapy (CRT) between 2003 and 2011 were eligible. The primary outcome was OS, and secondary endpoints included OS for high-risk (T4 and/or N3 disease) and human papillomavirus (HPV) subsets. RESULTS: Of the 14,856 analyzed patients, 78% and 22% received CRT and IC, respectively. With a median follow-up for surviving patients of 44 months, the 5-year OS probability for the entire cohort was 66% (66% CRT vs. 64% IC, p=0.022). Multivariable survival analysis showed no significant difference between CRT and IC (hazard ratio, HR, 0.95 for IC, p=0.255), and sensitivity analyses to adjust for immortal time bias brought the HR to 1.0 (p=0.859). There was also no OS difference for high-risk patients. There was a trend in favor of CRT for HPV-positive OPSCC (HR 1.63 with IC, p=0.064), with a significant OS benefit for HPV-negative, high-risk OPSCC (HR 0.63, p=0.048). CONCLUSION: For the vast majority of patients, including HPV-positive individuals, there was no difference in OS with IC, arguing for CRT to remain as the standard therapy. Subset analysis revealed a small cohort of aggressive cancer (T4/N3 HPV-negative) which may benefit from from IC, although selection bias could not be ruled out.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioterapia de Inducción/métodos , Neoplasias Orofaríngeas/tratamiento farmacológico , Infecciones por Papillomavirus/complicaciones , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/radioterapia , Papillomaviridae , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVES: Patients with advanced non-small cell lung cancer (NSCLC) have a life expectancy of less than 1 year. Therefore, it is important to maximize their quality of life and find a tool that can more accurately predict survival. MATERIALS: The Palliative Performance Scale (PPS) is used to predict survival for patients with advanced disease based on functional dimensions. The value of the PPS in ambulatory patients with cancer has not been examined to date. The Lung Cancer Symptom Scale (LCSS) measures six major symptoms and their effect on symptomatic distress and activity. We evaluated 62 patients with stage III or IV NSCLC and Eastern Cooperative Oncology Group (ECOG) Scale Score ≥1 at baseline in a thoracic oncology clinic. In all, 62 patients had LCSS and PPS evaluated at baseline and 54 patients had 4-week follow-up using LCSS, PPS, and ECOG. RESULTS: Fifty-four patients completed baseline and follow-up. Mean age was 63.7 years. Sixty-three percent were receiving chemotherapy at evaluation. Seventeen patients died. Mean baseline measures were LCSS 6.18 (1-14); PPS 66.6 (40-90); and ECOG 1.82 (1-4). Censored survival times were calculated from enrollment of the first patient for 380 days. A proportional hazardous model was computed for survival status. Hazard ratios for death were 1.25 (P = .013) for LCSS, 2.12 (P = .027) for ECOG, and 1.02 for PPS (P = .49). CONCLUSIONS: The LCSS predicted prognosis best in this study. The PPS did not accurately predict prognosis in our patient population.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Cuidados Paliativos/métodos , Actividades Cotidianas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Dieta , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Estadificación de Neoplasias , Pronóstico , Calidad de VidaRESUMEN
INTRODUCTION: The benefit of surgery (trimodality therapy [TMT]) after chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer (NSCLC) is controversial, but nodal pathologic complete response (N-PCR) is accepted as a strong predictor of overall survival (OS). We compared the outcomes of patients treated with TMT versus CRT, focusing on the importance of N-PCR. METHODS: Patients with stage III NSCLC treated with CRT or TMT from December 2004 through December 2012 were included; patients with N3 disease were excluded. Pathologic nodal response dichotomized surgical patients into N-PCR versus residual nodal disease (RND) groups. Actuarial OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) were compared between patients treated with CRT and TMT and between CRT and N-PCR/RND. RESULTS: The cohort was composed of 138 patients (52% CRT and 48% TMT). The median OS was significantly higher after TMT than after CRT (81 versus 31.8 mo, p = 0.0068). This benefit was restricted to N-PCR (n = 50, 83.2 versus 31.8 mo, p = 0.0004), as RND (n = 19) experienced poor OS (16.1 mo). On multivariable analyses, N-PCR had superior OS (hazard ratio [HR], 0.38; p = 0.0012), PFS (HR, 0.42; p = 0.0005), and DMFS (HR, 0.42; p = 0.0007) compared with CRT. Conversely, there were trends for worse OS and PFS for RND versus CRT, although only inferior DMFS was significant (HR, 1.83; p = 0.04). CONCLUSIONS: Surgical patients with complete nodal clearance experienced superior survival, but those with RND fared no better than CRT alone. Mediastinal response may play an important role in the decision to proceed with surgical resection after CRT for stage III NSCLC.